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Nrf2 AND carnosic acid

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https://www.readbyqxmd.com/read/27906174/therapeutic-advantage-of-pro-electrophilic-drugs-to-activate-the-nrf2-are-pathway-in-alzheimer-s-disease-models
#1
Stuart A Lipton, Tayebeh Rezaie, Anthony Nutter, Kevin M Lopez, James Parker, Kunio Kosaka, Takumi Satoh, Scott R McKercher, Eliezer Masliah, Nobuki Nakanishi
Alzheimer's disease (AD) is characterized by synaptic and neuronal loss, which occurs at least partially through oxidative stress induced by oligomeric amyloid-β (Aβ)-peptide. Carnosic acid (CA), a chemical found in rosemary and sage, is a pro-electrophilic compound that is converted to its active form by oxidative stress. The active form stimulates the Keap1/Nrf2 transcriptional pathway and thus production of phase 2 antioxidant enzymes. We used both in vitro and in vivo models. For in vitro studies, we evaluated protective effects of CA on primary neurons exposed to oligomeric Aβ...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27834734/nano-liquid-chromatography-orbitrap-ms-based-quantitative-proteomics-reveals-differences-between-the-mechanisms-of-action-of-carnosic-acid-and-carnosol-in-colon-cancer-cells
#2
Alberto Valdés, Virginia García-Cañas, Konstantin A Artemenko, Carolina Sim Oacute, Jonas Bergquist, Alejandro Cifuentes
Carnosic acid (CA) and carnosol (CS) are two structurally related diterpenes present in rosemary herb (Rosmarinus officinalis). Although several studies have demonstrated that both diterpenes can scavenge free radicals and interfere in cellular processes such as cell proliferation, they may not necessarily exert the same effects at the molecular level. In this work, a shotgun proteomics study based on stable isotope dimethyl labeling (DML) and nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) has been performed to identify the relative changes in proteins and to gain some light on the specific molecular targets and mechanisms of action of CA and CS in HT-29 colon cancer cells...
November 10, 2016: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/27686076/carnosic-acid-protects-mitochondria-of-human-neuroblastoma-sh-sy5y-cells-exposed-to-paraquat-through-activation-of-the-nrf2-ho-1axis
#3
Marcos Roberto de Oliveira, Alessandra Peres, Gustavo Costa Ferreira, Patrícia Fernanda Schuck, Clarissa S Gama, Simone Morelo Dal Bosco
Carnosic acid (CA; C20H28O4), which is also called salvin, is a major phenolic diterpene found in Rosmarinus officinalis L. and exhibits antioxidant, anti-inflammatory, and antiproliferative properties. CA activates the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor, leading to the upregulation of antioxidant and phase II detoxification enzymes, such as heme oxygenase-1 (HO-1), glutathione reductase (GR), γ-glutamate-cysteine ligase (γ-GCL), and glutathione S-transferase (GST), among others...
September 29, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27435046/carnosic-acid-protects-starvation-induced-sh-sy5y-cell-death-through-erk1-2-and-akt-pathways-autophagy-and-foxo3a
#4
Sachi Shibata, Hiroyuki Ishitobi, Shigeru Miyaki, Tomohiro Kawaoka, Tomoko Kayashima, Kiminori Matsubara
Carnosic acid (CA) is recognized as a unique neuroprotective compound in the herb rosemary, since it induces expression of antioxidant enzymes including heme oxygenase-1 (HO-1), γ-glutamylcysteine synthase (γ-GCS), and glutathione S-transferase (GST) via activation of nuclear factor erythroid 2-related factor 2 (Nrf2), which is a nuclear transcription factor. In this study, we examined the cytoprotective effects of CA against starvation. We found that CA protected starvation-induced SH-SY5Y cell death by activating Akt and extracellular signal-regulated kinase 1/2 (Erk1/2)...
December 2016: International Journal of Food Sciences and Nutrition
https://www.readbyqxmd.com/read/27317373/nrf2-activation-ameliorates-cytotoxic-effects-of-arsenic-trioxide-in-acute-promyelocytic-leukemia-cells-through-increased-glutathione-levels-and-arsenic-efflux-from-cells
#5
Shoichi Nishimoto, Toshihiro Suzuki, Shin Koike, Bo Yuan, Norio Takagi, Yuki Ogasawara
Carnosic acid (CA), a phenolic diterpene isolated from Rosmarinus officinalis, has been shown to activate nuclear transcription factor E2-related factor 2 (Nrf2), which plays a central role in cytoprotective responses to oxidative and electrophilic stress. Recently, the Nrf2-Kelch ECH associating protein 1 (Keap1) pathway has been associated with cancer drug resistance attributable to modulation of the expression and activation of antioxidant and detoxification enzymes. However, the exact mechanisms by which Nrf2 activation results in chemoresistance are insufficiently understood to date...
August 15, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27083155/carnosic-acid-affords-mitochondrial-protection-in-chlorpyrifos-treated-sh-sy5y-cells
#6
Marcos Roberto de Oliveira, Alessandra Peres, Gustavo Costa Ferreira, Patrícia Fernanda Schuck, Simone Morelo Dal Bosco
Carnosic acid (CA; C20H28O4) is a phenolic diterpene found in rosemary (Rosmarinus officinalis L.) and exhibits protective properties, e.g., antioxidant, anti-inflammatory, antitumor, and antimicrobial activities. In this context, CA has been viewed as a neuroprotective agent due to its ability in rescuing neuronal cells from pro-oxidant and pro-apoptotic challenges. In the present work, we found that CA pretreatment at 1 µM for 12 h suppressed the mitochondria-related pro-oxidant and mitochondria-dependent pro-apoptotic effects of chlorpyrifos (CPF) in human neuroblastoma SH-SY5Y cells...
October 2016: Neurotoxicity Research
https://www.readbyqxmd.com/read/26820671/molecular-and-biochemical-evidence-on-the-protective-effects-of-embelin-and-carnosic-acid-in-isoproterenol-induced-acute-myocardial-injury-in-rats
#7
COMPARATIVE STUDY
Cengiz Kocak, Fatma Emel Kocak, Raziye Akcilar, Ozben Ozden Isiklar, Havva Kocak, Zeynep Bayat, Hasan Simsek, Figen Taser, Irfan Altuntas
AIMS: Acute myocardial infarction is a serious acute cardiac disorder and heart disease is still a major public health problem in adults. We investigated the effects of embelin (EMB) and carnosic acid (CA) in animals with isoproterenol (ISO)-induced myocardial injury. MAIN METHODS: Adult male Wistar-Albino rats were divided into four groups: control, ISO, ISO with EMB, and ISO with CA. Before myocardial injury was induced, drugs were administered by oral gavage...
February 15, 2016: Life Sciences
https://www.readbyqxmd.com/read/26807019/carnosic-acid-protects-against-acetaminophen-induced-hepatotoxicity-by-potentiating-nrf2-mediated-antioxidant-capacity-in-mice
#8
Qi Guo, Zhiyang Shen, Hongxia Yu, Gaofeng Lu, Yong Yu, Xia Liu, Pengyuan Zheng
Acetaminophen (APAP) overdose is one of the most common causes of acute liver failure. The study aimed to investigate the protective effect of carnosic acid (CA) on APAP-induced acute hepatotoxicity and its underlying mechanism in mice. To induce hepatotoxicity, APAP solution (400 mg/kg) was administered into mice by intraperitoneal injection. Histological analysis revealed that CA treatment significantly ameliorated APAP-induced hepatic necrosis. The levels of both alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum were reduced by CA treatment...
January 2016: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/26730179/modulation-of-neurotrophic-signaling-pathways-by-polyphenols
#9
REVIEW
Fatemeh Moosavi, Razieh Hosseini, Luciano Saso, Omidreza Firuzi
Polyphenols are an important class of phytochemicals, and several lines of evidence have demonstrated their beneficial effects in the context of a number of pathologies including neurodegenerative disorders such as Alzheimer's and Parkinson's disease. In this report, we review the studies on the effects of polyphenols on neuronal survival, growth, proliferation and differentiation, and the signaling pathways involved in these neurotrophic actions. Several polyphenols including flavonoids such as baicalein, daidzein, luteolin, and nobiletin as well as nonflavonoid polyphenols such as auraptene, carnosic acid, curcuminoids, and hydroxycinnamic acid derivatives including caffeic acid phentyl ester enhance neuronal survival and promote neurite outgrowth in vitro, a hallmark of neuronal differentiation...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/26686574/protective-effect-of-carnosic-acid-against-paraquat-induced-redox-impairment-and-mitochondrial-dysfunction-in-sh-sy5y-cells-role-for-pi3k-akt-nrf2-pathway
#10
Marcos Roberto de Oliveira, Gustavo Costa Ferreira, Patrícia Fernanda Schuck
Carnosic acid (CA) is a phenolic diterpene isolated from Rosmarinus officinalis and exerts anti-inflammatory, antioxidant, and anticarcinogenic activities in different cell types. It has been reported that CA is able to cause protective effects on experimental models of neurodegeneration. However, the exact mechanism by which CA prevents neuronal degeneration remains to be better studied. We investigated here whether there is a role for CA as a neuroprotective agent in a paraquat (PQ) model of Parkinson's disease (PD) regarding cellular and mitochondrial-related redox parameters...
April 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/26577515/role-for-the-pi3k-akt-nrf2-signaling-pathway-in-the-protective-effects-of-carnosic-acid-against-methylglyoxal-induced-neurotoxicity-in-sh-sy5y-neuroblastoma-cells
#11
Marcos Roberto de Oliveira, Gustavo Costa Ferreira, Patrícia Fernanda Schuck, Simone Morelo Dal Bosco
Glycation, a process that occurs endogenously and generates advanced glycation end products (AGEs), presents an important role in cases of neurodegeneration, as for instance Alzheimer's disease (AD). Methylglyoxal (MG), a dicarbonyl compound, is the most potent inducer of AGEs, whose levels have been found increased in samples obtained from subjects suffering from AD. Moreover, MG induces protein cross-linking and redox impairment in vitro and in vivo. Carnosic acid (CA), a phenolic diterpene isolated from Rosmarinus officinalis, exerts protective effects in neuronal cells by increasing antioxidant defenses and detoxification systems...
December 5, 2015: Chemico-biological Interactions
https://www.readbyqxmd.com/read/26293030/carnosol-is-a-potent-lung-protective-agent-experimental-study-on-mice
#12
T Kawamura, T Momozane, M Sanosaka, K Sugimura, O Iida, H Fuchino, S Funaki, Y Shintani, M Inoue, M Minami, N Kawahara, H Takemori, M Okumura
INTRODUCTION: Oxidative stress has been implicated in various disease states and ischemia/reperfusion injury is a direct consequence of oxidative stress in lung transplantation. Because the success rate of organ transplantation in which ischemia/reperfusion is inevitable is highly influenced by oxidative stress, development of strategies to control oxidative stress would be beneficial. Here we identified natural compounds to reduce oxidative stresses in isolated mouse lungs. METHODS: We screened compounds associated with antioxidative stress in 200 plant extracts by monitoring the activities of nuclear factor erythroid 2-related factor 2 (NRF2)...
July 2015: Transplantation Proceedings
https://www.readbyqxmd.com/read/26223904/carnosic-acid-protects-normal-mouse-hepatocytes-against-h2-o2-induced-cytotoxicity-via-sirtuin-1-mediated-signaling
#13
Ting Wang, Yasuhiro Takikawa
AIM: Carnosic acid (CA) is well known for its antioxidant properties. The aim of this study was to examine the effects of CA on cytotoxicity under oxidative stress. METHODS: Primary hepatocytes and AML12 cells were treated with: (i) 0.1 μM, 1 μM and 10 μM CA; (ii) 3 mM H2 O2 with or without 1 μM CA; or (iii) 3 mM H2 O2 with 1 μM CA and 0.04 μM sirtuin 1 (SIRT1) inhibitor EX527 or 10 μM mitogen-activated protein kinase (MAPK) inhibitor U0126. Cell viability, intracellular reactive oxygen species (ROS) and lactate dehydrogenase (LDH) leakage were determined...
February 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/25974399/induction-of-the-pi-class-of-glutathione-s-transferase-by-carnosic-acid-in-rat-clone-9-cells-via-the-p38-nrf2-pathway
#14
COMPARATIVE STUDY
Chia-Yuan Lin, Chi-Rei Wu, Shu-Wei Chang, Yu-Jung Wang, Jia-Jiuan Wu, Chia-Wen Tsai
Induction of phase II enzymes is important in cancer chemoprevention. We compared the effect of rosemary diterpenes on the expression of the pi class of glutathione S-transferase (GSTP) in rat liver Clone 9 cells and the signaling pathways involved. Culturing cells with 1, 5, 10, or 20 μM carnosic acid (CA) or carnosol (CS) for 24 h in a dose-dependent manner increased the GSTP expression. CA was more potent than CS. The RNA level and the enzyme activity of GSTP were also enhanced by CA treatment. Treatment with 10 μM CA highly induced the reporter activity of the enhancer element GPEI...
June 2015: Food & Function
https://www.readbyqxmd.com/read/25744415/redox-dependent-induction-of-antioxidant-defenses-by-phenolic-diterpenes-confers-stress-tolerance-in-normal-human-skin-fibroblasts-insights-on-replicative-senescence
#15
Ana C Carvalho, Andreia C Gomes, Cristina Pereira-Wilson, Cristovao F Lima
Mild stress-induced hormesis represents a promising strategy for targeting the age-related accumulation of molecular damage and, therefore, for preventing diseases and achieving healthy aging. Fruits, vegetables, and spices contain a wide variety of hormetic phytochemicals, which may explain the beneficial health effects associated with the consumption of these dietary components. In the present study, the induction of cellular antioxidant defenses by the phenolic diterpenes carnosic acid (CA) and carnosol (CS) were studied in normal human skin fibroblasts, and insights into the aging process at the cellular level investigated...
June 2015: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/25692407/protection-from-cyanide-induced-brain-injury-by-the-nrf2-transcriptional-activator-carnosic-acid
#16
Dongxian Zhang, Brian Lee, Anthony Nutter, Paul Song, Nima Dolatabadi, James Parker, Sara Sanz-Blasco, Traci Newmeyer, Rajesh Ambasudhan, Scott R McKercher, Eliezer Masliah, Stuart A Lipton
Cyanide is a life-threatening, bioterrorist agent, preventing cellular respiration by inhibiting cytochrome c oxidase, resulting in cardiopulmonary failure, hypoxic brain injury, and death within minutes. However, even after treatment with various antidotes to protect cytochrome oxidase, cyanide intoxication in humans can induce a delayed-onset neurological syndrome that includes symptoms of Parkinsonism. Additional mechanisms are thought to underlie cyanide-induced neuronal damage, including generation of reactive oxygen species...
June 2015: Journal of Neurochemistry
https://www.readbyqxmd.com/read/25432068/nrf2-are-activator-carnosic-acid-decreases-mitochondrial-dysfunction-oxidative-damage-and-neuronal-cytoskeletal-degradation-following-traumatic-brain-injury-in-mice
#17
Darren M Miller, Indrapal N Singh, Juan A Wang, Edward D Hall
The importance of free radical-induced oxidative damage after traumatic brain injury (TBI) has been well documented. Despite multiple clinical trials with radical-scavenging antioxidants that are neuroprotective in TBI models, none is approved for acute TBI patients. As an alternative antioxidant target, Nrf2 is a transcription factor that activates expression of antioxidant and cytoprotective genes by binding to antioxidant response elements (AREs) within DNA. Previous research has shown that neuronal mitochondria are susceptible to oxidative damage post-TBI, and thus the current study investigates whether Nrf2-ARE activation protects mitochondrial function when activated post-TBI...
February 2015: Experimental Neurology
https://www.readbyqxmd.com/read/24903830/carnosic-acid-promotes-myocardial-antioxidant-response-and-prevents-isoproterenol-induced-myocardial-oxidative-stress-and-apoptosis-in-mice
#18
Bidya Dhar Sahu, Uday Kumar Putcha, Madhusudana Kuncha, Shyam Sunder Rachamalla, Ramakrishna Sistla
UNLABELLED: Carnosic acid is a well-known antioxidant. Recently, it has been identified as modulator of nuclear factor erythroid 2-related factor 2 (Nrf2). The effect of carnosic acid in the context of cardiovascular disorders has not been studied. In the present study, we investigated the beneficial effect and the underlying cardioprotective mechanism of carnosic acid by using mouse model of isoproterenol (ISO)-induced myocardial stress. Elevated serum levels of Troponin I, CK-MB, LDH, SGOT and SGPT, and myofibrillar degeneration with necrotic damage, and the presence of epicardial inflammatory infiltrate (H & E staining) confirmed the ISO-induced myocardial stress...
September 2014: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/24262357/reprint-of-nrf2-are-mediated-antioxidant-actions-of-pro-electrophilic-drugs
#19
Takumi Satoh, Scott R McKercher, Stuart A Lipton
Living cells maintain a balance between oxidation and reduction, and perturbations of this redox balance are thought to contribute to various diseases. Recent attempts to regulate redox state have focused on electrophiles (EPs), which activate potent cellular defense systems against oxidative stress. One example of this approach is exemplified by carnosic acid (CA) and carnosol (CS), compounds that are found in the herb rosemary (Rosmarinus officinalis). Importantly, CA and CS themselves are not electrophilic, but in response to oxidation, become electrophilic, and then activate the Keap1/Nrf2/ARE (antioxidant-response element) transcription pathway to synthesize endogenous antioxidant "phase 2"enzymes...
January 2014: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/23892355/nrf2-are-mediated-antioxidant-actions-of-pro-electrophilic-drugs
#20
REVIEW
Takumi Satoh, Scott R McKercher, Stuart A Lipton
Living cells maintain a balance between oxidation and reduction, and perturbations of this redox balance are thought to contribute to various diseases. Recent attempts to regulate redox state have focused on electrophiles (EPs), which activate potent cellular defense systems against oxidative stress. One example of this approach is exemplified by carnosic acid (CA) and carnosol (CS), compounds that are found in the herb rosemary (Rosmarinus officinalis). Importantly, CA and CS themselves are not electrophilic, but in response to oxidation, become electrophilic, and then activate the Keap1/Nrf2/ARE (antioxidant-response element) transcription pathway to synthesize endogenous antioxidant "phase 2" enzymes...
December 2013: Free Radical Biology & Medicine
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